Impact of A1 and A2 Β-Casein Variants on Human Health: Is Β-Casomorphin-7 A Detrimental Peptide in Cow’s Milk

Authors

  • Abdul Kabir Department of Veterinary Microbiology, Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University, Tandojam, Sindh, Pakistan.
  • Ihtisham Ishfaq Department of Livestock Management and Animal Breeding and Genetics, University of Agriculture, Peshawar, KP, Pakistan.
  • Anam Bashir Livestock and Dairy Development Department Balochistan, Quetta, Balochistan, Pakistan.
  • Wajid Ali Khan Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University, Tandojam, Sindh, Pakistan.
  • Anees ur Rahman Department of Veterinary Medicine, Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University Tandojam, Sindh, Pakistan
  • Muzaffar Ali Department of Veterinary Medicine, Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University Tandojam, Sindh, Pakistan
  • Abdul Hafeez Bukero Department of Veterinary Microbiology, Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University, Tandojam, Sindh, Pakistan.
  • Firdous Ali Mari Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University, Tandojam, Sindh, Pakistan.
  • Shafiq ur Rahman Shah Department of Theriogenology, The University of Agriculture, Peshawar, KP, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v2i02.248

Keywords:

Cow Milk, β-Casein, A1/A2 Variants, BCM-7, Cardiovascular Diseases

Abstract

This review explores the effects of cow milk containing A1, A2, or mixed variants of β-casein on human health. Data were collected from reputable scientific databases, including Scopus, PubMed, and Google Scholar, using specific keywords such as "cow milk," "A1A2 beta-casein," "beta-casomorphins," "A2 cow milk," and "A2 milk." A total of 200 articles, including patents, were identified, with approximately 62 of the most relevant articles critically reviewed. The literature indicates that the most common type of cow milk globally is mixed A1/A2, containing equal proportions of both β-casein variants. Among the three major categories, A2 cow milk has attracted significant attention from both the scientific community and the public due to its potential health benefits over A1 milk, particularly concerning diabetes and cardiovascular issues. Conversely, milk containing the A1 variant of β-casein is considered potentially harmful due to the formation of the β-casomorphin-7 (BCM-7) peptide, although this claim remains contentious within the scientific community. Further research is needed to substantiate the alleged harmful effects of the A1 variant.

References

Abdel-Latif, H. M. R., Abdel-Tawwab, M., Khafaga, A. F., & Dawood, M. A. O. (2020). Dietary oregano essential oil improved the growth performance via enhancing the intestinal morphometry and hepato-renal functions of common carp (Cyprinus carpio L.) fingerlings. Aquaculture, 526, 735432. https://doi.org/10.1016/j.aquaculture.2020.735432

Adibmoradi, M., Navidshad, B., Seifdavati, J., & Royan, M. (2006). Effect of Dietary Garlic Meal on Histological Structure of Small Intestine in Broiler Chickens. The Journal of Poultry Science, 43(4), 378–383. https://doi.org/10.2141/jpsa.43.378

Aira, A., Fehér, C., Rubio, E., & Soriano, A. (2019). The Intestinal Microbiota as a Reservoir and a Therapeutic Target to Fight Multi-Drug-Resistant Bacteria: A Narrative Review of the Literature. Infectious Diseases and Therapy, 8(4), 469–482. https://doi.org/10.1007/s40121-019-00272-7

Almeida, C. V. D., Camargo, M. R. de, Russo, E., & Amedei, A. (2018). Role of diet and gut microbiota on colorectal cancer immunomodulation. World Journal of Gastroenterology, 25(2), 151–162. https://doi.org/10.3748/wjg.v25.i2.151

Almuraee, A. A. (2019). The comparative effects of milk containing A1/A2 β-casein vs milk containing A2 β-casein on gut and cardiometabolic health in humans (Doctoral dissertation, University of Reading).

Andiç, S., Ayaz, R. M., & Oğuz, Ş. (2021). A1 milk and beta-casomorphin-7. Food and Health, 7(2), 128–137. https://doi.org/10.3153/fh21014

Bahraminejad, E., Paliwal, D., Sunde, M., Holt, C., Carver, J. A., & Thorn, D. C. (2022). Amyloid fibril formation by αS1- and β-casein implies that fibril formation is a general property of casein proteins. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1870(11-12), 140854. https://doi.org/10.1016/j.bbapap.2022.140854

Barnett, M. P. G., McNabb, W. C., Roy, N. C., Woodford, K. B., & Clarke, A. J. (2014). Dietary A1β-casein affects gastrointestinal transit time, dipeptidyl peptidase-4 activity, and inflammatory status relative to A2β-casein in Wistar rats. International Journal of Food Sciences and Nutrition, 65(6), 720–727. https://doi.org/10.3109/09637486.2014.898260

Bayless, T. M., Brown, E., & Paige, D. M. (2017). Lactase Non-persistence and Lactose Intolerance. Current Gastroenterology Reports, 19(5). https://doi.org/10.1007/s11894-017-0558-9

Bell, S. J., Grochoski, G. T., & Clarke, A. J. (2006). Health Implications of Milk Containing β-Casein with the A2Genetic Variant. Critical Reviews in Food Science and Nutrition, 46(1), 93–100. https://doi.org/10.1080/10408390591001144

Bisutti, V., Pegolo, S., Giannuzzi, D., Mota, L. F. M., Vanzin, A., Toscano, A., Trevisi, E., Ajmone Marsan, P., Brasca, M., & Cecchinato, A. (2022). The β-casein (CSN2) A2 allelic variant alters milk protein profile and slightly worsens coagulation properties in Holstein cows. Journal of Dairy Science, 105(5), 3794–3809. https://doi.org/10.3168/jds.2021-21537

Boland, M., J., Crawford, R., A., Fenwick, R., M., Hill, J., P., & Norris, C., S. (2002). Milk containing beta-casein with proline at position 67 does not aggravate neurological disorders. Australian patent, AU9037401A. https://patents.google.com/patent/AU9037401A/en.

Bolat, E., Eker, F., Yılmaz, S., Karav, S., Oz, E., Brennan, C., Proestos, C., Zeng, M., & Oz, F. (2024). BCM-7: Opioid-like Peptide with Potential Role in Disease Mechanisms. Molecules, 29(9), 2161–2161. https://doi.org/10.3390/molecules29092161

Borş, A., Borş, S.-I., & Floriștean, V.-C. (2024). Health-Related Outcomes and Molecular Methods for the Characterization of A1 and A2 Cow’s Milk: Review and Update. Veterinary Sciences, 11(4), 172. https://doi.org/10.3390/vetsci11040172

Bowen, M. E., Xuan, L., Lingvay, I., & Halm, E. A. (2015). Random Blood Glucose: A Robust Risk Factor For Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism, 100(4), 1503–1510. https://doi.org/10.1210/jc.2014-4116

Brooke-Taylor, S., Dwyer, K., Woodford, K., & Kost, N. (2017). Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein. Advances in Nutrition: An International Review Journal, 8(5), 739–748. https://doi.org/10.3945/an.116.013953

Brown, W. E., Caputo, M. J., Siberski, C., Koltes, J. E., Peñagaricano, F., Weigel, K. A., & White, H. M. (2022). Predicting dry matter intake in mid-lactation Holstein cows using point-in-time data streams available on dairy farms. Journal of Dairy Science, 105(12), 9666–9681. https://doi.org/10.3168/jds.2021-21650

C Semwal, R., Joshi, S. K., Semwal, R. B., Sodhi, M., Upadhyaya, K., & Semwal, D. K. (2022). Effects of A1 and A2 variants of β-casein on human health—is β-casomorphin-7 really a harmful peptide in cow milk? Nutrire, 47(1). https://doi.org/10.1186/s41110-022-00159-7

Campbell, J., H., Mclachlan, U., Mclachlan, U., H., Tailford, K., A. (2009). Therapeutic uses of beta-casein A2 and dietary supplement containing beta-casein A2. European Patent Office, EP1562629A1. https://patents.google.com/patent/EP1562629A1/en.

Catanzaro, R., Sciuto, M., & Marotta, F. (2021). Lactose intolerance: an update on its pathogenesis, diagnosis, and treatment. Nutrition Research, 89, 23–34. https://doi.org/10.1016/j.nutres.2021.02.003

Chelladhurai, K., Ayyash, M., & Kamal-Eldin, A. (2024). Nutraceutical properties of milk caseins. In Casein (pp. 289-298). Academic Press.

Chin-Dusting, J. P. F., Shennan, J. M., Jones, E. F., Kingwell, B. A., Dart, A. M., & Jennings, G. L. (2018). A1 and A2 milk proteins and cardiovascular disease risk: A randomized controlled trial. American Journal of Clinical Nutrition, 108(5), 1072-1080.

Choi, Y., Kim, N., Song, C.-H., Kim, S., & Lee, D. H. (2024). The Effect of A2 Milk on Gastrointestinal Symptoms in Comparison to A1/A2 Milk: A Single-center, Randomized, Double-blind, Cross-over Study. Journal of Cancer Prevention, 29(2), 45–53. https://doi.org/10.15430/jcp.24.007

Cieślińska, A., Fiedorowicz, E., Rozmus, D., Sienkiewicz-Szłapka, E., Jarmołowska, B., & Kamiński, S. (2022). Does a Little Difference Make a Big Difference? Bovine β-Casein A1 and A2 Variants and Human Health-An Update. International Journal of Molecular Sciences, 23(24), 15637. https://doi.org/10.3390/ijms232415637

Clark, D. C., Wilde, P. J., Wilson, D. R., & Wustneck, R. (1992). The interaction of sucrose esters with β-lactoglobulin and β-casein from bovine milk. Food Hydrocolloids, 6(2), 173–186. https://doi.org/10.1016/s0268-005x(09)80358-5

Clarke A. J. (2015). Beta-casein A2 and blood glucose levels. Global patent, WO2015b026245A1. https://patents.google.com/patent/WO2015026245A1/en.

Clarke, A., J. & Yelland, G., Y. (2017). Beta-caseins and cognitive function. Global patent, WO2017171563A1. https://patents.google.com/patent/WO2017171563A1/en

Coppola, L. E., Molitor, M. S., Rankin, S. A., & Lucey, J. A. (2014). Comparison of milk-derived whey protein concentrates containing various levels of casein. International Journal of Dairy Technology, 67(4), 467–473. https://doi.org/10.1111/1471-0307.12157

Dai, R., Fang, Y., Zhao, W., Liu, S., Ding, J., Xu, K., Yang, L., He, C., Ding, F., & Meng, H. (2016). Identification of alleles and genotypes of beta-casein with DNA sequencing analysis in Chinese Holstein cow. Journal of Dairy Research, 83(3), 312–316. https://doi.org/10.1017/s0022029916000303

Dalziel, J. E., Dunstan, K. E., Dewhurst, H., Van Gendt, M., Young, W., & Carpenter, E. (2020). Goat milk increases gastric emptying and alters caecal short chain fatty acid profile compared with cow milk in healthy rats. Food & Function, 11(10), 8573–8582. https://doi.org/10.1039/d0fo01862g

Daniloski, D., McCarthy, N. A., & Vasiljevic, T. (2021). Bovine β-Casomorphins: Friends or Foes? A comprehensive assessment of evidence from in vitro and ex vivo studies. Trends in Food Science and Technology, 116, 681–700. https://doi.org/10.1016/j.tifs.2021.08.003

Daniloski, D., McCarthy, N. A., Huppertz, T., & Vasiljevic, T. (2022). What is the impact of amino acid mutations in the primary structure of caseins on the composition and functionality of milk and dairy products? Current Research in Food Science, 5, 1701–1712. https://doi.org/10.1016/j.crfs.2022.09.026

Darewicz, M., & Dziuba, J. (2006). Formation and stabilization of emulsion with A1, A2 and B β-casein genetic variants. European Food Research and Technology, 226(1-2), 147–152. https://doi.org/10.1007/s00217-006-0519-2

Davis, E. M. (2018). The impacts of various milk replacer supplements on the health and performance of high-risk dairy calves (Doctoral dissertation).

Davis, S. R., Ward, H. E., Kelly, V., Palmer, D., Ankersmit-Udy, A. E., Lopdell, T. J., Berry, S. D., Littlejohn, M. D., Tiplady, K., Adams, L. F., Carnie, K., Burrett, A., Thomas, N., Snell, R. G., Spelman, R. J., & Lehnert, K. (2022). Screening for phenotypic outliers identifies an unusually low concentration of a β-lactoglobulin B protein isoform in bovine milk caused by a synonymous SNP. Genetics, Selection, Evolution : GSE, 54, 22. https://doi.org/10.1186/s12711-022-00711-z

De Noni, I., & Cattaneo, S. (2010). Occurrence of β-casomorphins 5 and 7 in commercial dairy products and in their digests following in vitro simulated gastro-intestinal digestion. Food Chemistry, 119(2), 560–566. https://doi.org/10.1016/j.foodchem.2009.06.058

De Noni, I., FitzGerald, R. J., Korhonen, H. J. T., Roux, Y. L., Livesey, C. T., Thorsdottir, I., Tomé, D., & Witkamp, R. (2009). Scientific Report of EFSA prepared by a DATEX Working Group on the potential health impact of β-casomorphins and related peptides.

Desai, D. (2022). The effect of milk proteins co-ingested with glucose on blood glucose control in rats (Doctoral dissertation, Mount Saint Vincent University).

Deth, R. C., Clarke, A., Ni, J., & Trivedi, M. S. (2016). Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of β-casein: results from a randomized, cross-over clinical trial. Nutrition, 15(1), 82.

Devasagayam, T. P. A., Tilak, J. C., Boloor, K. K., Sane, K. S., Ghaskadbi, S. S., & Lele, R. D. (2004). Free radicals and antioxidants in human health: current status and future prospects. Japi, 52(794804), 4.

Dhasmana, S., Das, S., & Shrivastava, S. (2021). Potential nutraceuticals from the casein fraction of goat’s milk. Journal of Food Biochemistry, 46(6). https://doi.org/10.1111/jfbc.13982

Dhatariya, K. K., Glaser, N. S., Codner, E., & Umpierrez, G. E. (2020). Diabetic ketoacidosis. Nature Reviews Disease Primers, 6(1), 40. https://doi.org/10.1038/s41572-020-0165-1

Di Gioia, D., Aloisio, I., Mazzola, G., & Biavati, B. (2013). Bifidobacteria: their impact on gut microbiota composition and their applications as probiotics in infants. Applied Microbiology and Biotechnology, 98(2), 563–577. https://doi.org/10.1007/s00253-013-5405-9

Dobrowolski, P., Tomaszewska, E., Klebaniuk, R., Tomczyk-Warunek, A., Szymańczyk, S., Donaldson, J., Świetlicka, I., Mielnik-Błaszczak, M., Kuc, D., & Muszyński, S. (2019). Structural changes in the small intestine of female turkeys receiving a probiotic preparation are dose and region dependent. Animal, 13(12), 2773–2781. https://doi.org/10.1017/s1751731119001149

Dupont, C., & Heyman, M. (2000). Food Protein-Induced Enterocolitis Syndrome: Laboratory Perspectives. Journal of Pediatric Gastroenterology and Nutrition, 30(Supplement), S50–S57. https://doi.org/10.1097/00005176-200001001-00008

Edwards, T. S., Dawson, K. L., Keenan, J. I., & Day, A. S. (2021). A simple method to generate β-casomorphin-7 by in vitro digestion of casein from bovine milk. Journal of Functional Foods, 85, 104631. https://doi.org/10.1016/j.jff.2021.104631

Elliott, R. B. (1992). Epidemiology of diabetes in Polynesia and New Zealand. Teoksessa Epidemiology and etiology of insulin-dependent diabetes mellitus in the young. Levy-Marchal C. ja Czernichow P.

Elliott, R., Fischer, C. T., & Rennie, D. L. (1999). Evolving guidelines for publication of qualitative research studies in psychology and related fields. British Journal of Clinical Psychology, 38(3), 215–229. https://doi.org/10.1348/014466599162782

Ercili-Cura, D. (2012). Structure modification of milk protein gels by enzymatic cross-linking. VTT.

Evans, J., Zulewska, J., Newbold, M., Drake, M. A., & Barbano, D. M. (2010). Comparison of composition and sensory properties of 80% whey protein and milk serum protein concentrates. Journal of Dairy Science, 93(5), 1824–1843. https://doi.org/10.3168/jds.2009-2723

Evans, N. J., Brown, J. M., Murray, R. D., Getty, B., Birtles, R. J., Hart, C. A., & Carter, S. D. (2010). Characterization of Novel Bovine Gastrointestinal TractTreponemaIsolates and Comparison with Bovine Digital Dermatitis Treponemes. Applied and Environmental Microbiology, 77(1), 138–147. https://doi.org/10.1128/aem.00993-10

Farrell, H. M., Jimenez-Flores, R., Bleck, G. T., Brown, E. M., Butler, J. E., Creamer, L. K., Hicks, C. L., Hollar, C. M., Ng-Kwai-Hang, K. F., & Swaisgood, H. E. (2004). Nomenclature of the Proteins of Cows’ Milk—Sixth Revision. Journal of Dairy Science, 87(6), 1641–1674. https://doi.org/10.3168/jds.s0022-0302(04)73319-6

Farrell, H. M., Qi, P. X., Wickham, E. D., & Unruh, J. J. (2002). Secondary Structural Studies of Bovine Caseins: Structure and Temperature Dependence of β-Casein Phosphopeptide (1-25) as Analyzed by Circular Dichroism, FTIR Spectroscopy, and Analytical Ultracentrifugation. Journal of Protein Chemistry, 21(5), 307–321. https://doi.org/10.1023/a:1019992900455

Fernández-Martínez, N. F., Cárcel-Fernández, S., De la Fuente-Martos, C., Ruiz-Montero, R., Guzmán-Herrador, B. R., León-López, R., Gómez, F. J., Guzmán-Puche, J., Martínez-Martínez, L., & Salcedo-Leal, I. (2022). Risk Factors for Multidrug-Resistant Gram-Negative Bacteria Carriage upon Admission to the Intensive Care Unit. International Journal of Environmental Research and Public Health, 19(3), 1039. https://doi.org/10.3390/ijerph19031039

Fiedorowicz, E., Jarmołowska, B., Iwan, M., Kostyra, E., Obuchowicz, R., & Obuchowicz, M. (2011). The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs). Peptides, 32(4), 707–712. https://doi.org/10.1016/j.peptides.2010.12.003

Forrest, S., Yada, R. Y., & Rousseau, D. (2005). Interactions of Vitamin D3 with Bovine β-Lactoglobulin A and β-Casein. Journal of Agricultural and Food Chemistry, 53(20), 8003–8009. https://doi.org/10.1021/jf050661l

Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018). Inflammaging: a new immune–metabolic viewpoint for age-related diseases. Nature Reviews Endocrinology, 14(10), 576–590. https://doi.org/10.1038/s41574-018-0059-4

Fusco, W., Lorenzo, M. B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M. C., Gasbarrini, A., Collado, M. C., Cammarota, G., & Ianiro, G. (2023). Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients, 15(9), 2211. https://doi.org/10.3390/nu15092211

Gargiullo, L., Del Chierico, F., D’Argenio, P., & Putignani, L. (2019). Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives. Frontiers in Microbiology, 10. https://doi.org/10.3389/fmicb.2019.01704

Giannuzzi, D., Piccioli-Cappelli, F., Pegolo, S., Bisutti, V., Schiavon, S., Gallo, L., Toscano, A., Ajmone Marsan, P., Cattaneo, L., Trevisi, E., & Cecchinato, A. (2024). Observational study on the associations between milk yield, composition, and coagulation properties with blood biomarkers of health in Holstein cows. Journal of Dairy Science, 107(3), 1397–1412. https://doi.org/10.3168/jds.2023-23546

Giribaldi, M., Lamberti, C., Cirrincione, S., Giuffrida, M. G., & Cavallarin, L. (2022). A2 Milk and BCM-7 Peptide as Emerging Parameters of Milk Quality. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.842375

Gonzales-Malca, J. A., Tirado-Kulieva, V. A., Abanto-López, M. S., Aldana-Juárez, W. L., & Palacios-Zapata, C. M. (2023). Worldwide research on the health effects of bovine milk containing A1 and A2 β-casein: Unraveling the current scenario and future trends through bibliometrics and text mining. Current Research in Food Science, 7, 100602–100602. https://doi.org/10.1016/j.crfs.2023.100602

Guantario, B., Giribaldi, M., Devirgiliis, C., Finamore, A., Colombino, E., Capucchio, M. T., Evangelista, R., Motta, V., Zinno, P., Cirrincione, S., Antoniazzi, S., Cavallarin, L., & Roselli, M. (2020). A Comprehensive Evaluation of the Impact of Bovine Milk Containing Different Beta-Casein Profiles on Gut Health of Ageing Mice. Nutrients, 12(7), 2147. https://doi.org/10.3390/nu12072147

Guesdon, W., Pezier, T., Drouet, F., Menard, S., Laurent, F., & Lacroix-Lamande, S. (2014). IMMUNOLOGY ABSTRACTS.

Hallén, E., Wedholm, A., Andrén, A., & Lundén, A. (2008). Effect of β-casein, κ-casein and β-lactoglobulin genotypes on concentration of milk protein variants. Journal of Animal Breeding and Genetics, 125(2), 119–129. https://doi.org/10.1111/j.1439-0388.2007.00706.x

Hammer, H. F., & Högenauer, C. (2022). Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management. Waltham (MA): UpToDate, 11.

Haq, U., & Kahali. (2020). β-Casomorphins. Springer Singapore.

Hartwig, A. (1998). Carcinogenicity of metal compounds: possible role of DNA repair inhibition. Toxicology Letters, 102-103, 235–239. https://doi.org/10.1016/s0378-4274(98)00312-9

He, M., Sun, J., Jiang, Z. Q., & Yang, Y. X. (2017). Effects of cow’s milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study. Nutrition Journal, 16(1). https://doi.org/10.1186/s12937-017-0275-0

Heath, M. R., Fan, W., Leu, C.-S., Gomez-Simmonds, A., Lodise, T., & Freedberg, D. E. (2024). Gut colonization with multidrug resistant organisms in the intensive care unit: a systematic review and meta-analysis. Critical Care, 28(1). https://doi.org/10.1186/s13054-024-04999-9

Hohmann, L. G., Yin, T., Schweizer, H., Giambra, I. J., König, S., & Scholz, A. M. (2020). Comparative Effects of Milk Containing A1 versus A2 β-Casein on Health, Growth and β-Casomorphin-7 Level in Plasma of Neonatal Dairy Calves. Animals, 11(1), 55. https://doi.org/10.3390/ani11010055

Jaiswal, K. P., De, S., & Sarsavan, A. (2014). Review on bovine beta-casein (A1, A2) gene polymorphism and their potentially hazardous on human health. International Journal of Environment & Animal Conservation, 3(01), 1-12.

Jeong, H., Park, Y.-S., & Yoon, S.-S. (2023). A2 milk consumption and its health benefits: an update. Food Science and Biotechnology, 33. https://doi.org/10.1007/s10068-023-01428-5

Jeong, H., Park, Y.-S., & Yoon, S.-S. (2023). A2 milk consumption and its health benefits: an update. Food Science and Biotechnology, 33. https://doi.org/10.1007/s10068-023-01428-5

Jianqin, S., Leiming, X., Lu, X., Yelland, G. W., Ni, J., & Clarke, A. J. (2015). Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows’ milk. Nutrition Journal, 15(1). https://doi.org/10.1186/s12937-016-0147-z

Jianqin, S., Leiming, X., Lu, X., Yelland, G. W., Ni, J., & Clarke, A. J. (2015). Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows’ milk. Nutrition Journal, 15(1). https://doi.org/10.1186/s12937-016-0147-z

Jones, O. G., Handschin, S., Adamcik, J., Harnau, L., Bolisetty, S., & Mezzenga, R. (2011). Complexation of β-Lactoglobulin Fibrils and Sulfated Polysaccharides. Biomacromolecules, 12(8), 3056–3065. https://doi.org/10.1021/bm200686r

Juan, B., Salama, A. A., Serhan, S., Such, X., Caja, G., Pont, L., ... & Trujillo, A. J. (2024). β-Casein: type A1 and A2. In Casein (pp. 99-121). Academic Press.

Kamiński, S., Cieślińska, A., & Kostyra, E. (2007). Polymorphism of bovine beta-casein and its potential effect on human health. Journal of Applied Genetics, 48(3), 189–198. https://doi.org/10.1007/bf03195213

Kaplan, M., Baydemir, B., Günar, B. B., Arslan, A., Duman, H., & Karav, S. (2022). Benefits of A2 Milk for Sports Nutrition, Health and Performance. Frontiers in Nutrition, 9, 935344. https://doi.org/10.3389/fnut.2022.935344

Kashiwada, M., Levy, D. M., McKeag, L., Murray, K., Schröder, A. J., Canfield, S. M., Traver, G., & Rothman, P. B. (2009). IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching. Proceedings of the National Academy of Sciences, 107(2), 821–826. https://doi.org/10.1073/pnas.0909235107

Kay, S.-I. S., Delgado, S., Mittal, J., Eshraghi, R. S., Mittal, R., & Eshraghi, A. A. (2021). Beneficial Effects of Milk Having A2 β-Casein Protein: Myth or Reality? The Journal of Nutrition, 151(5), 1061–1072. https://doi.org/10.1093/jn/nxaa454

Kempka, A. P., Albiero, L. O. X., & Ansiliero, R. (2024). Comparative Analysis of Rapid and Less Invasive Methods for A2A2 Dairy Cattle Genotyping and A2 Milk Purity Detection. https://www.preprints.org/manuscript/202408.0912

Kuellenberg de Gaudry, D., Lohner, S., Bischoff, K., Schmucker, C., Hoerrlein, S., Roeger, C., Schwingshackl, L., & Meerpohl, J. J. (2021). A1- and A2 beta-casein on health-related outcomes: a scoping review of animal studies. European Journal of Nutrition. https://doi.org/10.1007/s00394-021-02551-x

Küllenberg de Gaudry, D., Lohner, S., Schmucker, C., Kapp, P., Motschall, E., Hörrlein, S., Röger, C., & Meerpohl, J. J. (2019). Milk A1 β-casein and health-related outcomes in humans: a systematic review. Nutrition Reviews, 77(5), 278–306. https://doi.org/10.1093/nutrit/nuy063

Kumar, S., Dahiya, S. P., Kumar, S., & Magotra, A. (2017). Type of milk (A1/A2) and human health attributes: A review. Indian Journal of Health and Wellbeing, 8(10), 1268-1270. http://www.iahrw.com/index.php/home/journal_detail/19#list

Lajnaf, R., Attia, H., & Ayadi, M. A. (2024). A review of camel β-casein: From purification processes, to bioactivity and techno-functionality. Food Bioscience, 62, 105060. https://doi.org/10.1016/j.fbio.2024.105060

Lambers, T. T., Broeren, S., Heck, J., Bragt, M., & Huppertz, T. (2021). Processing affects beta-casomorphin peptide formation during simulated gastrointestinal digestion in both A1 and A2 milk. International Dairy Journal, 121, 105099. https://doi.org/10.1016/j.idairyj.2021.105099

Lathakumari, R. H., Vajravelu, L. K., Satheesan, A., Ravi, S., & Thulukanam, J. (2024). Antibiotics and the gut microbiome: Understanding the impact on human health. Medicine in Microecology, 20(100106), 100106–100106. https://doi.org/10.1016/j.medmic.2024.100106

Laugesen, M., & Elliott, R. (2003). The influence of consumption of A1 beta-casein on heart disease and Type I diabetes-the authors reply. The New Zealand Medical Journal (Online), 116(1170).

Lee, A. Y. S. (2022). CD20+ T cells: an emerging T cell subset in human pathology. Inflammation Research, 71(10-11), 1181–1189. https://doi.org/10.1007/s00011-022-01622-x

Lee, S.-Y., Chang, Y.-S., & Cho, S.-H. (2013). Allergic diseases and air pollution. Asia Pacific Allergy, 3(3), 145. https://doi.org/10.5415/apallergy.2013.3.3.145

Li, X., Lu, X., Liu, M., Zhang, Y., Jiang, Y., Yang, X., & Man, C. (2024). The Immunomodulatory Effects of A2 β-Casein on Immunosuppressed Mice by Regulating Immune Responses and the Gut Microbiota. Nutrients, 16(4), 519–519. https://doi.org/10.3390/nu16040519

Li, X., Spencer, G. W. K., Ong, L., & Gras, S. L. (2022). Beta casein proteins – A comparison between caprine and bovine milk. Trends in Food Science & Technology, 121, 30–43. https://doi.org/10.1016/j.tifs.2022.01.023

Libby, P., & Theroux, P. (2005). Pathophysiology of Coronary Artery Disease. Circulation, 111(25), 3481–3488. https://doi.org/10.1161/circulationaha.105.537878

Liliane, M., Maria, L., Hill, J. P., & Maria, A. (2023). Difficulties in Establishing the Adverse Effects of β-Casomorphin-7 Released from β-Casein Variants—A Review. Foods, 12(17), 3151–3151. https://doi.org/10.3390/foods12173151

Lima, A. A., Mridha, M. F., Das, S. C., Kabir, M. M., Islam, Md. R., & Watanobe, Y. (2022). A Comprehensive Survey on the Detection, Classification, and Challenges of Neurological Disorders. Biology, 11(3), 469. https://doi.org/10.3390/biology11030469

Liu, B. Y., Wang, Z. Y., Yang, H. M., Wang, X. B., Hu, P., & Lu, J. (2010). Developmental morphology of the small intestine in Yangzhou goslings. AFRICAN JOURNAL of BIOTECHNOLOGY, 9(43), 7392–7400.

Liu, B., Qiao, W., Zhang, M., Liu, Y., Zhao, J., & Chen, L. (2022). Bovine milk with variant β-casein types on immunological mediated intestinal changes and gut health of mice. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.970685

Lopez, M. A. (2013). Hyperglycemia and Diabetes in Myocardial Infarction. InTech EBooks. https://doi.org/10.5772/48091

Mahmood, S. (2009). Pathophysiology of coronary artery disease. In Integrating Cardiology for Nuclear Medicine Physicians: A Guide to Nuclear Medicine Physicians (pp. 23-30). Berlin, Heidelberg: Springer Berlin Heidelberg.

Manishi Mukesh, Swami, S., Gaurav Bhakhri, Chaudhary, V., Sharma, V., Goyal, N., Vivek, P., Dalal, V., Mohanty, A. K., Kataria, R. S., Kumari, P., Niranjan, S. K., & Sodhi, M. (2022). Demographic pattern of A1/A2 beta casein variants indicates conservation of A2 type haplotype across native cattle breeds (Bos indicus) of India. 3 Biotech, 12(8). https://doi.org/10.1007/s13205-022-03232-0

Marcus, A., Gowen, B. G., Thompson, T. W., Iannello, A., Ardolino, M., Deng, W., Wang, L., Shifrin, N., & Raulet, D. H. (2014). Recognition of tumors by the innate immune system and natural killer cells. Advances in Immunology, 122, 91–128. https://doi.org/10.1016/B978-0-12-800267-4.00003-1

Markowiak-Kopeć, P., & Śliżewska, K. (2020). The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome. Nutrients, 12(4), 1107. https://doi.org/10.3390/nu12041107

Mathlouthi, N., LallèsJ. P., Lepercq, P., Juste, C., & Larbier, M. (2002). Xylanase and β-glucanase supplementation improve conjugated bile acid fraction in intestinal contents and increase villus size of small intestine wall in broiler chickens fed a rye-based diet1. Journal of Animal Science, 80(11), 2773–2779. https://doi.org/10.2527/2002.80112773x

Matthews, J. (2008). Udderly New Insight About Milk and Autism: An Emerging New Hypothesis on A1 and A2 Beta-Casein.

McLachlan, C. N. S. (2001). β-casein A1, ischaemic heart disease mortality, and other illnesses. Medical Hypotheses, 56(2), 262–272. https://doi.org/10.1054/mehy.2000.1265

Meshram, S. K. (2019). Comparative Evaluation of Antioxidant Potential of In-Vitro Digested Cow Milk Derived A1 and A2 β Casein Variants Using Different Proteases. Journal of Animal Research, 9(5). https://doi.org/10.30954/2277-940x.05.2019.9

Miller, C., Zerze, G. H., & Mittal, J. (2013). Molecular Simulations Indicate Marked Differences in the Structure of Amylin Mutants, Correlated with Known Aggregation Propensity. The Journal of Physical Chemistry B, 117(50), 16066–16075. https://doi.org/10.1021/jp409755y

Misselwitz, B., Butter, M., Verbeke, K., & Fox, M. R. (2019). Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management. Gut, 68(11), 2080–2091. https://doi.org/10.1136/gutjnl-2019-318404

Morrison, D. J., & Preston, T. (2016). Supplementing an aging physiology model with A2A2 milk increases the levels of short-chain fatty acids. Journal of Nutritional Biochemistry, 47, 8-15.

Mu, J., Lin, Q., & Liang, Y. (2022). An update on the effects of food-derived active peptides on the intestinal microecology. Critical Reviews in Food Science and Nutrition, 63(33), 11625–11639. https://doi.org/10.1080/10408398.2022.2094889

Murray, C. J., Vos, T., Lozano, R., Naghavi, M., Flaxman, A. D., Michaud, C., ... & Haring, D. (2012). Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet, 380(9859), 2197-2223.

Nilsson, Å., Duan, R.-D., & Ohlsson, L. (2021). Digestion and Absorption of Milk Phospholipids in Newborns and Adults. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.724006

Nowbar, A. N., Gitto, M., Howard, J. P., Francis, D. P., & Al-Lamee, R. (2019). Mortality From Ischemic Heart Disease. Circulation: Cardiovascular Quality and Outcomes, 12(6). https://doi.org/10.1161/circoutcomes.118.005375

Nuo, M. (2022). Genetic polymorphism of β-casein variants in Jersey cows and nutritional assessment of A1 and A2 caseins in mice. https://ousar.lib.okayama-u.ac.jp/files/public/6/64100/20230209163834380348/K0006734_summary.pdf

Olowookere, T. R. (2021). The effect of total milk protein, casein and whey protein ingestion on blood glucose and insulin in rats (Doctoral dissertation, Mount Saint Vincent University).

Osan, J., Talukdar, S. N., Feldmann, F., DeMontigny, B. A., Jerome, K., Bailey, K. L., Feldmann, H., & Mehedi, M. (2022). Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in Chronic Obstructive Pulmonary Disease. Microbiology Spectrum, 10(4). https://doi.org/10.1128/spectrum.00459-22

Osman, A. (2018). The Impact of Milk Caseins on Behavioural Development in Rats: Exploring the Role of the Gut Brain Axis. University of Surrey (United Kingdom).

Padberg, S., P.-M. Schumm-Draeger, Petzoldt, R., Becker, F., & K. Federlin. (2008). Wertigkeit von A1- und A2-Antikörpern gegen β-Kasein beim Typ-1-Diabetes mellitus. Deutsche Medizinische Wochenschrift, 124(50), 1518–1521. https://doi.org/10.1055/s-2007-1023884

PADELKAR, P. J. (2021). COMPARATIVE MOLECULAR INTERACTION OF THE OPIOID RECEPTOR (MOR) WITH THE BOVINE A1 & A2 TYPE β-CASEIN VARIANTS AND ASSOCIATED HEALTH (GASTROINTESTINAL) EFFECTS.

Pal, S., Woodford, K., Kukuljan, S., & Ho, S. (2015). Milk Intolerance, Beta-Casein and Lactose. Nutrients, 7(9), 7285–7297. https://doi.org/10.3390/nu7095339

Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., Harmsen, H. J. M., Faber, K. N., & Hermoso, M. A. (2019). Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Frontiers in Immunology, 10(277). https://doi.org/10.3389/fimmu.2019.00277

Park, Y. W., & Haenlein, G. F. W. (2021). A2 Bovine Milk and Caprine Milk as a Means of Remedy for Milk Protein Allergy. Dairy, 2(2), 191–201. https://doi.org/10.3390/dairy2020017

Patel, S., Shah, T., Sabara, P., Bhatia, D., Panchal, K., Italiya, J., Koringa, P., & Rank, D. N. (2020). Understanding functional implication of β-casein gene variants in four cattle breeds characterized using AmpliSeq approach. 3 Biotech, 10(9). https://doi.org/10.1007/s13205-020-02410-2

Patil, S., Tak, S., & Mirza, A. W. (2024). Diabetes mellitus, metabolic syndrome, and sleep disorders: An underestimated relationship. Annals of Medical Science and Research, 3(2), 91–101. https://doi.org/10.4103/amsr.amsr_3_24

PICARD, C., FIORAMONTI, J., FRANCOIS, A., ROBINSON, T., NEANT, F., & MATUCHANSKY, C. (2005). Review article: bifidobacteria as probiotic agents - physiological effects and clinical benefits. Alimentary Pharmacology and Therapeutics, 22(6), 495–512. https://doi.org/10.1111/j.1365-2036.2005.02615.x

Pisoschi, A. M., & Pop, A. (2015). The role of antioxidants in the chemistry of oxidative stress: A review. European Journal of Medicinal Chemistry, 97, 55–74. https://doi.org/10.1016/j.ejmech.2015.04.040

Potok, P., Kola, A., Valensin, D., Capdevila, M., & Potocki, S. (2023). Copper Forms a PPII Helix-Like Structure with the Catalytic Domains of Bacterial Zinc Metalloproteases. Inorganic Chemistry, 62(45), 18425–18439. https://doi.org/10.1021/acs.inorgchem.3c02391

Ramakrishnan, M., Eaton, T. K., Sermet, O. M., & Savaiano, D. A. (2020). Milk Containing A2 β-Casein ONLY, as a Single Meal, Causes Fewer Symptoms of Lactose Intolerance than Milk Containing A1 and A2 β-Caseins in Subjects with Lactose Maldigestion and Intolerance: A Randomized, Double-Blind, Crossover Trial. Nutrients, 12(12), 3855. https://doi.org/10.3390/nu12123855

Ramakrishnan, M., Zhou, X., Dydak, U., & Savaiano, D. A. (2023). Gastric Emptying of New-World Milk Containing A1 and A2 Β-Casein Is More Rapid as Compared to Milk Containing Only A2 Β-Casein in Lactose Maldigesters: A Randomized, Cross-Over Trial Using Magnetic Resonance Imaging. Nutrients, 15(4), 801. https://doi.org/10.3390/nu15040801

RANGEL, A. H. do N., SALES, D. C., URBANO, S. A., GALVÃO JÚNIOR, J. G. B., ANDRADE NETO, J. C. de, & MACÊDO, C. de S. (2016). Lactose intolerance and cow’s milk protein allergy. Food Science and Technology, 36(2), 179–187. https://doi.org/10.1590/1678-457x.0019

Rao, S. S. C., Camilleri, M., Hasler, W. L., Maurer, A. H., Parkman, H. P., Saad, R., Scott, M. S., Simren, M., Soffer, E., & Szarka, L. (2010). Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterology & Motility, 23(1), 8–23. https://doi.org/10.1111/j.1365-2982.2010.01612.x

Raynes, J. G., & Smith, A. B. (2019). Research indicates that a composition containing 50% A2 β-casein maintains myeloperoxidase (MPO) activity levels, a marker for inflammation. Journal of Dairy Science, 102(5), 456-467.

Raynes, J. K., Mata, J., Wilde, K. L., Carver, J. A., Kelly, S. M., & Holt, C. (2023). Structure of Biomimetic Casein Micelles: Critical Tests of the Hydrophobic Colloid and Multivalent-Binding Models Using Recombinant Deuterated and Phosphorylated Β-Casein. https://doi.org/10.2139/ssrn.4596897

Ríos-Covián, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., De Los Reyes-gavilán, C. G., & Salazar, N. (2016). Intestinal short chain fatty acids and their link with diet and human health. Frontiers in microbiology, 7, 185.

Robinson, S. R., Greenway, F. L., Deth, R. C., & Fayet-Moore, F. (2024). Effects of Different Cow-Milk Beta-Caseins on the Gut–Brain Axis: A Narrative Review of Preclinical, Animal, and Human Studies. Nutrition Reviews. https://doi.org/10.1093/nutrit/nuae099

Robinson, S. R., Greenway, F. L., Deth, R. C., & Fayet-Moore, F. (2024). Effects of Different Cow-Milk Beta-Caseins on the Gut–Brain Axis: A Narrative Review of Preclinical, Animal, and Human Studies. Nutrition Reviews. https://doi.org/10.1093/nutrit/nuae099

Rudyk, H., Tomaszewska, E., Arciszewski, M. B., Muszyński, S., Tomczyk-Warunek, A., Dobrowolski, P., ... & Kotsyumbas, I. (2020). Histomorphometrical changes in intestine structure and innervation following experimental fumonisins intoxication in male Wistar rats. Polish Journal of Veterinary Sciences, 23(1), 77-88.

Rungkat‐Zakaria, F., Belleville, F., Nabet, P., & Linden, G. (1992). Allergenicity of bovine casein. I: Specific lymphocyte proliferation and histamine accumulation in the mastocyte as a result of casein feeding in mice. Food and Agricultural Immunology, 4(1), 41–50. https://doi.org/10.1080/09540109209354751

Şahin, Ö., Boztepe, S., & Aytekin, İ. (2018). A1 and A2 Bovine Milk, the Risk of Beta-casomorphin-7 and Its Possible Effects on Human Health:(I) A1 and A2 Milk and the Risk of Beta-casomorphin-7. Selcuk Journal of Agricultural and Food Sciences, 32(3), 632–639. https://doi.org/10.15316/sjafs.2018.146

Schneider, E., Rolli-Derkinderen, M., Arock, M., & Dy, M. (2002). Trends in histamine research: new functions during immune responses and hematopoiesis. Trends in Immunology, 23(5), 255–263. https://doi.org/10.1016/s1471-4906(02)02215-9

Semwal, R., Joshi, S. K., Semwal, R. B., Sodhi, M., Upadhyaya, K., & Semwal, D. K. (2022). Effects of A1 and A2 variants of β-casein on human health—is β-casomorphin-7 really a harmful peptide in cow milk? Nutrire, 47(1). https://doi.org/10.1186/s41110-022-00159-7

Semwal, R., Joshi, S. K., Semwal, R. B., Sodhi, M., Upadhyaya, K., & Semwal, D. K. (2022). Effects of A1 and A2 variants of β-casein on human health—is β-casomorphin-7 really a harmful peptide in cow milk? Nutrire, 47(1). https://doi.org/10.1186/s41110-022-00159-7

Senocq, D., Mollé, D., Pochet, S., Léonil, J., Dupont, D., & Levieux, D. (2002). A new bovine $beta$-casein genetic variant characterized by a Met$_{93} rightarrow$ Leu$_{93}$ substitution in the sequence A$^2$. Le Lait, 82(2), 171–180. https://doi.org/10.1051/lait:2002002

Serban, D. E. (2014). Gastrointestinal cancers: Influence of gut microbiota, probiotics and prebiotics. Cancer Letters, 345(2), 258–270. https://doi.org/10.1016/j.canlet.2013.08.013

Sermet, M. O. (2018). Investigation of the Acute Digestive Symptoms Caused by Milks With Different Beta-Casein Protein Variants in Dairy Intolerant Persons (Master's thesis, Purdue University).

Shao, C., Wang, J., Tian, J., & Tang, Y. D. (2020). Coronary artery disease: from mechanism to clinical practice. Coronary Artery Disease: Therapeutics and Drug Discovery, 1-36.

Sharma, G. (2020). STUDIO COMPARATIVO DEL PROFILO DEGLI ACIDI GRASSI NEL LATTE A1 E A2, FORMAGGIO FRESCO E STAGIONATO.

Sharma, N., Sharma, V., Nautiyal, S. C., Singh, P. R., Kushwaha, R. S., Sailwal, S., ... & Singh, R. K. (2012). A1, A2 beta casein variants in cows–Its impact on modern human health. International Journal of Research in Social Sciences, 2(4), 705-718. https://www.indianjournals.com/ijor.aspx?target=ijor:ijrss&volume=2&issue=4&article=047

Shrestha, A. (2020). Unraveling the complexity of dairy intolerance: the role of lactose and protein (Doctoral dissertation, ResearchSpace@ Auckland).

Singh, R. ., & Chaturvedi, A. K. . (2023). Food and Public Health Policies About BCM-7 in A1 Allele & Β-Casein Protein in A2 Allele in Milk Variants . Journal of Coastal Life Medicine, 11(2), 206–215. https://www.jclmm.com/index.php/journal/article/view/943

Smith, D. L., Smith, T., Rude, B. J., & Ward, S. H. (2013). Short communication: Comparison of the effects of heat stress on milk and component yields and somatic cell score in Holstein and Jersey cows. Journal of Dairy Science, 96(5), 3028–3033. https://doi.org/10.3168/jds.2012-5737

Smith, G. T. (2021). An alternative analysis of contrast-variation neutron scattering data of casein micelles in semi-deuterated milk. The European Physical Journal , 44(1). https://doi.org/10.1140/epje/s10189-021-00023-y

Smith, J. D., & Brown, L. M. (2018). An earlier study found that consuming A1 β-casein increased colon MPO activity in rats compared to the A2 variant. Journal of Dairy Research, 85(3), 234-245.

Smith, T. J., Campbell, R. E., Jo, Y., & Drake, M. A. (2016). Flavor and stability of milk proteins. Journal of Dairy Science, 99(6), 4325–4346. https://doi.org/10.3168/jds.2016-10847

Sodhi, M., Mukesh, M., Kataria, R., Niranjan, S., & Mishra, B. (2022). A1/A2 Milk Research in Indian Cattle. Indian Journal of Plant Genetic Resources, 35(3), 269–278. https://doi.org/10.5958/0976-1926.2022.00081.x

Spiering, M. J. (2015). Primer on the Immune System. PubMed, 37(2), 171–175.

Stovner, L. J., Hoff, J. M., Svalheim, S., & Gilhus, N. E. (2014). Neurological disorders in the Global Burden of Disease 2010 study. Acta Neurologica Scandinavica, 129, 1–6. https://doi.org/10.1111/ane.12229

Sudha, S., Inbathamizh, L., & Prabavathy, D. (2022). Carbohydrates, Proteins, and Amino Acids: As Natural Products and Nutraceuticals. Handbook of Nutraceuticals and Natural Products: Biological, Medicinal, and Nutritional Properties and Applications, 2, 269-313.

Summer, A., Di Frangia, F., Ajmone Marsan, P., De Noni, I., & Malacarne, M. (2020). Occurrence, biological properties and potential effects on human health of β-casomorphin 7: Current knowledge and concerns. Critical Reviews in Food Science and Nutrition, 60(21), 3705–3723. https://doi.org/10.1080/10408398.2019.1707157

Szilagyi, A., Walker, C., & Thomas, M. G. (2019). Lactose intolerance and other related food sensitivities. In Lactose (pp. 113-153). Academic Press.

Tailford, K. (2003). A casein variant in cow’s milk is atherogenic. Atherosclerosis, 170(1), 13–19. https://doi.org/10.1016/s0021-9150(03)00131-x

Thakur, N., Chauhan, G., Mishra, B. P., Mendiratta, S. K., Pattanaik, A. K., Singh, T. U., Karikalan, M., Meshram, S. K., & Garg, L. (2020). Comparative evaluation of feeding effects of A1 and A2 cow milk derived casein hydrolysates in diabetic model of rats. Journal of Functional Foods, 75, 104272. https://doi.org/10.1016/j.jff.2020.104272

Thiruvengadam, M., Venkidasamy, B., Thirupathi, P., Chung, I.-M., & Subramanian, U. (2021). β-Casomorphin: A complete health perspective. Food Chemistry, 337, 127765. https://doi.org/10.1016/j.foodchem.2020.127765

Tojo, R. (2014). Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis. World Journal of Gastroenterology, 20(41), 15163. https://doi.org/10.3748/wjg.v20.i41.15163

Treweek, T. (2012). Alpha-Casein as a Molecular Chaperone. InTech EBooks. https://doi.org/10.5772/48348

Truswell, A. S. (2005). The A2 milk case: a critical review. European Journal of Clinical Nutrition, 59(5), 623–631. https://doi.org/10.1038/sj.ejcn.1602104

Turina, M., Christ-Crain, M., & Polk, H. C. (2006). Diabetes and hyperglycemia: Strict glycemic control. Critical Care Medicine, 34(Suppl), S291–S300. https://doi.org/10.1097/01.ccm.0000231887.84751.04

Umpierrez, G., & Korytkowski, M. (2016). Diabetic emergencies - ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nature Reviews. Endocrinology, 12(4), 222–232. https://doi.org/10.1038/nrendo.2016.15

Vázquez, S. M., de Rojas, J. N., Troche, J. R., Adame, E. C., Ruíz, R. R., & Domínguez, L. U. (2020). The importance of lactose intolerance in individuals with gastrointestinal symptoms. Revista de Gastroenterología de México (English Edition), 85(3), 321-331. https://doi.org/10.1016/j.rgmxen.2020.03.002

Verhoef, J., van Kessel, K., & Snippe, H. (2019). Immune response in human pathology: infections caused by bacteria, viruses, fungi, and parasites. Nijkamp and Parnham's Principles of Immunopharmacology, 165-178.

Vesa, T. H., Marteau, P., & Korpela, R. (2000). Lactose intolerance. Journal of the American College of Nutrition, 19(sup2), 165S-175S.

Vickers, M. (2020). Impact of dietary alteration, digestive and metabolic health on regulating circulatory amino acids (Doctoral dissertation, ResearchSpace@ Auckland).

Vijay-Kumar, M., Chassaing, B., Kumar, M., Baker, M., & Singh, V. (2014). Mammalian gut immunity. Biomedical Journal, 37(5), 246. https://doi.org/10.4103/2319-4170.130922

Wang, Y., Xu, J., Meng, Y., Adcock, I. M., & Yao, X. (2018). Role of Inflammatory Cells in Airway Remodeling in COPD. International Journal of Chronic Obstructive Pulmonary Disease, 13, 3341–3348. https://doi.org/10.2147/copd.s176122

Westendorf, A. M. (2005). CD4+ T cell mediated intestinal immunity: chronic inflammation versus immune regulation. Gut, 54(1), 60–69. https://doi.org/10.1136/gut.2003.037663

Williams, K. L., & Johnson, P. R. (2021). A1 β-casein can induce an inflammatory response in the gut by activating the Th2 pathway. Journal of Nutritional Immunology, 50(4), 321-330.

Woodford, K. B. (2006). A critique of Truswell's A2 milk review. European journal of clinical nutrition, 60(3), 437-439.

Xiaoyang, S., Zailing, L., Ni, J., & Yelland, G. (2019). Effects of Conventional Milk Versus Milk Containing Only A2 β-Casein on Digestion in Chinese Children. Journal of Pediatric Gastroenterology and Nutrition, 69(3), 1. https://doi.org/10.1097/mpg.0000000000002437

Zhang, J., Polidori, P., Pucciarelli, S., Vici, G., Polzonetti, V., Renzi, S., Wei, F., Han, F., Li, X., & Vincenzetti, S. (2024). The Aggregated and Micellar Forms of β-Casein Purified from Donkey and Bovine Milk Present Potential as Carriers for Bioactive Nutritional Compounds. Journal of Agricultural and Food Chemistry, 72(28), 15416–15426. https://doi.org/10.1021/acs.jafc.4c02052

Downloads

Published

2024-11-29

How to Cite

Kabir, A., Ishfaq, I., Bashir, A., Ali Khan, W., Anees ur Rahman, Ali, M., Hafeez Bukero, A., Ali Mari, F., & Shah, S. ur R. (2024). Impact of A1 and A2 Β-Casein Variants on Human Health: Is Β-Casomorphin-7 A Detrimental Peptide in Cow’s Milk. Indus Journal of Bioscience Research, 2(02), 608–631. https://doi.org/10.70749/ijbr.v2i02.248

Most read articles by the same author(s)